Knocking out barriers to engineered cell activity

  title={Knocking out barriers to engineered cell activity},
  author={Jennifer R. Hamilton and Jennifer A. Doudna},
  pages={976 - 977}
CRISPR-Cas9 gene-edited T cells show safety and long-term engraftment in humans Engineered T cell therapies are revolutionizing cancer treatment by achieving long-lasting remission in blood-related cancers, such as leukemia and lymphoma. These therapies involve removal of patient T cells, “reprogramming” them to attack cancer cells, and then transferring them back into the patient. Targeted gene inactivation (knockout) using CRISPR-Cas9 can enhance T cell activity (1, 2) and has the potential… 
Trends in CRISPR-Cas9 technology application in cancer.
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Delivery technologies for T cell gene editing: Applications in cancer immunotherapy
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Nanotechnology to advance CRISPR–Cas genetic engineering of plants
Major barriers preventing CRISPR-mediated plant genetic engineering from reaching its full potential are identified, and ways that nanoparticle technologies can lower or eliminate these barriers are discussed.
Anticipating and Identifying Collateral Damage in Genome Editing.
How to anticipate and detect genome editing events by a combination of assays to capture all possible genomic changes and strategies for preventing unwanted effects are discussed.
Variability in Genome Editing Outcomes: Challenges for Research Reproducibility and Clinical Safety
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  • 2021
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Receptor‐centric solutions for the opioid epidemic: Making the opioid user impervious to overdose death
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This mini‐review presents the view that contemporary approaches to stem the tide of opioid overdose deaths are insufficient to make a significant impact. Instead, a focus on the opioid receptor as


CRISPR-engineered T cells in patients with refractory cancer
This first-in-human, phase 1 clinical trial was designed to test the safety and feasibility of multiplex CRISPR-Cas9 gene editing of T cells from patients with advanced, refractory cancer and found the persistence of the T cells expressing the engineered TCR was much more durable than in three previous clinical trials during which T cells were infused.
Multiplex Genome Editing to Generate Universal CAR T Cells Resistant to PD1 Inhibition
Gene-disrupted allogeneic CAR and TCR T cells could provide an alternative as a universal donor to autologous T cells, which carry difficulties and high production costs.
CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells
Improved therapeutic efficacy of Cas9-edited CAR T cells is demonstrated and the potential of precision genome engineering to enhance next-generation cell therapies is highlighted.
Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection
It is demonstrated that directing a CD19-specific CAR to the T- cell receptor α constant (TRAC) locus not only results in uniform CAR expression in human peripheral blood T cells, but also enhances T-cell potency, with edited cells vastly outperforming conventionally generated CAR T cells in a mouse model of acute lymphoblastic leukaemia.
Optimized RNP transfection for highly efficient CRISPR/Cas9-mediated gene knockout in primary T cells
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    The Journal of experimental medicine
  • 2018
An optimized approach for Cas9/RNP transfection of primary mouse and human T cells without TCR stimulation that results in near complete loss of target gene expression at the population level, mitigating the need for selection is described.
Reprogramming human T cell function and specificity with non-viral genome targeting
A non-viral strategy to introduce large DNA sequences into T cells enables the correction of a pathogenic mutation that causes autoimmunity, and the replacement of an endogenous T-cell receptor with an engineered receptor that can recognize cancer antigens.
Identification of preexisting adaptive immunity to Cas9 proteins in humans
Together, these data demonstrate that there are preexisting humoral and cell-mediated adaptive immune responses to Cas9 in humans, a finding that should be taken into account as the CRISPR–Cas9 system moves toward clinical trials.
A Pilot Trial of the Combination of Transgenic NY-ESO-1–reactive Adoptive Cellular Therapy with Dendritic Cell Vaccination with or without Ipilimumab
ACT of fresh NY-ESO-1 transgenic T cells prepared via a short ex vivo protocol and given with DC vaccination, with or without ipilimumab, is feasible and results in transient antitumor activity, with no apparent clinical benefit of the addition of ipILimumab.
CAR T cell immunotherapy for human cancer
Opportunities and challenges for entering mainstream oncology that presently face the CAR T field are described, with a focus on the challenges that have emerged over the past several years.